Onc drugs

Cyclophosphamide

Alkylating agent, Nitrogen mustard

RBS: hemorrhagic cystitis, cardiotoxicity

Ifosamide

Alkylating agent, Nitrogen mustard

RBS: hemorrhagic cystitis, cardiotoxicity, encephalopathy

Cisplatin

Alkylating Agent, Platinum analog

Common: nephrotoxic, ototoxic, neurotoxic, metal taste

RBS: Anaphylaxis

Class - Alkylating agent

Non-cycle specific

MOA: monofuntional - damages DNA as it tries to repair alkylation. Bifunctional - cross-links DNA intrastrand or cross strand, preventing reading

Class toxicities: myelosuppression, N&V, infertility, alopecia, secondary malignancies (AML, MDS, other cancers)

Mercaptopurine

Anti-metabolite, purine analog

Common: hepatotoxic

RBS: TPMT deficiency, DDI w/ allopurinol & azathioprine, secondary malignancy (T-cell lymphomas)

Fluorouracil

Anti-metabolite, pyrimidine analog (converts to FUTP or FdUTP)

Common: GI toxicity

RBS: hand & foot syndrome, cardiotoxic

Antidote: uridine triacetate

Methotrexate

Anti-metabolite, folate antagonist

Dose dependant toxicities w/ clearance

Many DDIs

RBS: renal failure, hepatotoxic, derm toxic, pneumonitis, chemical arachnoiditis

Antidote: glucarpidase (carboxypeptidase)

Class - Anti-metabolite

Cycle-specific

MOA: substitute for natually occurring metabolites and structure components

Class toxicities: myelosuppression, mucositis

Doxorubicin (conventional)

Topoisomerase inhibitor, anthracycline

cycle-nonspecific

MOA: topo II inhibition, intercalate DNA base pairs, produce ROS

Common: body fluid discoloration, CINV

RBS: cardiotoxic, secondary malignacies (AML, MDS)

Etoposide

Topoisomerase inhibitor, epipodophyllotoxins

Cycle-specific: S and G2 phase

MOA: topo II inhibition, intercalate DNA base pairs, may inhibit mitochondrial transport

Common: hypotension (infusion-related)

RBS: Hypersensitivity reactions (avoid by switching to phosphate formulation)

Irinotecan (conventional)

Topoisomerase inhibitor, camptothecin

Cycle-specific: S phase

MOA: Topo I inhibition (reversible binding to topo I-DNA complex)

Common: diarrhea

Bleomycin

Topoisomerase inhibitor, other

Cycle-specific: G2 phase

MOA: causes single and double strand breaks in G-C rich portion of DNA. Not very active in blood due to bleomycin hydrolase. Has glycopeptide antibiotic action

Common: skin hyperpigmentation

RBS: pulmotoxin, hypersensitivity reactions

Class - topoisomerase inhibitor

cell-cycle specificity varies

MOA: interfere with DNA strand repair by Topo proteins

Class-wide toxicities: myelocupression, alopecia, infertility, vesicant (don’t give in peripheral veins)

Paclitaxel (conventional)

Anti-microtubule, taxane

Common: arthralgia/myalgia

RBS: hepatotoxic

Vincristine (conventional)

Anti-microtubule, vinca alkaloid

RBS: neurotoxic, GI toxic (constipaiton), hepatotoxic,

Fatal if given intrathecal (give in mini bag instead of syringe)

Class - Anti-microtubules

Cell-cycle specific: M phase

MOA: interferes with mitotic spindle, inhibiting cellular replication

Class-wide toxicities: peripheral neuropathy, alopecia, vesicant

Leuprolide

Hormonal agent, GnRH agonist (stimulate receptors to increase negative feedback cycle)

RBS: tumor flare (initial growth from agonism), cardiometabolic (hyperglycemia, diabetes, hyperlipidemia, etc), decrease bone mineral density

Degarelix

Hormonal agent, GnRH antagonist

Common: increased LFTs

Tamoxifen

Hormonal agent, antiestrogen (SERM, blocks signalling at breast tissue)

Common: vaginal discharge

RBS: thromboembolic events (DVT, stroke, etc.), ocular effects, secondary malignancies (uterine/endometrial cancer)

DDIs: CYP3A4 and 2D6

Bone mineral density protected after menopause, but decresed premenopause

Anastrozole

Hormonal agent, aromatase inhibitor (blocks androgen conversion to estradiol in tissues)

Common: arthralgia

RBS: decreased bone mineral density, hypercholesterolemia

Abiraterone

Hormonal agent, antiandrogen (block CYP17 during testosterone synthesis)

Common: mineralcorticoid excess, hypertriglyceridemia, increased LFTs

RBS: hepatotoxic, cardiovascular disease

Bicalutamide

Hormonal agent, antiandrogen (inhibit androgen receptor translocation)

Common: hypertriglyceridemia, increased LFTs

RBS: hepatotoxic, cardiovascular disease

Class - hormonal agent

MOA: manipulates endocrine system to ruduce hormone levels or block hormone action for hormone-mediated cancers

Class toxicities: hot flashes, sexual dysfunction, gynecomastia, edema, emotional lability, depression, GI toxic

Epidermal Growth Factor Receptor (EGFR) inhibitors

Cetuximab (Erbitux) - biologic; Erlotinib (Tarceva) - small molecule

MOA: binds to EGFR at ATP-binding site, blocking phosphorylation and subsequent downstream signalling. DOES NOT WORK IF KRAS IS MUTATED

Class-common: derm toxic (acneiform rash), diarrhea, paronychia

Class-RBS: interstitial lung disease, electrolyte disturbances (mAb only), hepatotoxic (TKI only), DDI CYP1A2 (TKI only)

HER2 Inhibitors

Trastuzumab (Herceptin & Herceptin Hylecta)

MOA: bind extracellular HER2 receptors, preventing dimerization and subsequent activation (mAbs); bind to intracellular domain of HER2, preventing downstream signalling (TKIs)

Class-common: fatigue, HA, weakness; TKI only: N&V, diarrhea, mucositis

Class-RBS: cardiomyopathy (reversible), birth defects

Agent-specfic: pulmotoxic, renal toxic

NOT interchangeable between formulations (eg. Herceptin vs Herceptin Hylecta vs ado-trastuzumab emtansine)

Anaplastic lymphoma kinase (ALK) inhibitors

Crizotinib (Xalkori)

MOA: targets fused/mutated ALK intracellularly, preventing downstream signalling

Common: emetic (mod-high risk), diarrhea OR constipation, anorexia, fatigue, vision problems

RBS: Hepatotoxic, bradycardia, interstitial lung disease, QTc prolongation

Vascular Endothelial Growth Factor (VEGF) inhibitors

Bevacizumab (Avastin)

MOA: neutralizes VEGF, preventing association with endothelial receptors and the growth of new veseels, reducing blood supply to tumor

Class-common: HTN, proteinuria, hemorrhage; TKI-specific: voice disorder, fatigue, hypothyroidism, emetic

Class-RBS: VTE, heart failure, GI perforation, slow wound healing; TKI-specific: hand-foot syndrome, hepatotoxic

BRAF and MEK inhibitors

BRAF: dabrafenib (Tafinlar); MEK: trametinib (Mekinist)

MOA: interferes with the ATP-binding site of each enzyme, preventing phosphorylation and subsequent downstream signalling

BRAF-common: derm toxic, arthralgia, alopecia, fatigue, HA

BRAF-RBS: ocular toxic, QTc prolongation, secondary malignancies (skin, head, neck cancers; risk reduced when used with MEKis)

MEK-common: derm toxic, diarrhea

MEK-RBS: cardiomyopathy, HTN, hemorrhage, hepatotoxic, ocular toxic

Poly ADP Ribose Polymerase (PARP) inhibitors

Olaparib (Lynparza)

MOA: inhibits PARP enzyme involved in the repair of single- and double-strand DNA breaks reliant on base excision repair and homologous recombination

Class-common: fatigue, N&V

Class-RBS: Increased SCr, myelosuppression, secondary malignancies (AML, MDS)